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Glucose‐lowering activity of the dipeptidyl peptidase‐4 inhibitor saxagliptin in drug‐naive patients with type 2 diabetes *
Author(s) -
Rosenstock J.,
Sankoh S.,
List J. F.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2008.00876.x
Subject(s) - saxagliptin , medicine , placebo , cohort , dipeptidyl peptidase 4 inhibitor , type 2 diabetes , postprandial , dipeptidyl peptidase 4 , incretin , pharmacology , endocrinology , diabetes mellitus , gastroenterology , sitagliptin , alternative medicine , pathology
Aim: Enhancing the physiologic actions of the endogenous incretin hormones, glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide, by inhibiting dipeptidyl peptidase‐4 (DPP‐4), the enzyme responsible for their degradation, is an emerging treatment for type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the safety and efficacy of dose ranges of the DPP‐4 inhibitor saxagliptin (BMS‐477118) in patients with T2DM. Methods: In a 12‐week, multicentre, randomized, parallel‐group, double‐blind, placebo‐controlled trial conducted at 152 out‐patient US study centres, 338 (low‐dose cohort) and 85 (high‐dose cohort) drug‐naive patients with T2DM and inadequate glycaemic control (baseline HbA1c ≥6.8 and ≤9.7%) were randomized. Following a 2‐week washout, patients received saxagliptin 2.5, 5, 10, 20 or 40 mg once daily, or placebo, for 12 weeks (low‐dose cohort). In a second cohort, patients received saxagliptin 100 mg once daily, or placebo, for 6 weeks (high‐dose cohort). The main outcome measure was saxagliptin dose response assessed as change from baseline in HbA1c following double‐blind treatment. Results: In all treatment arms, saxagliptin significantly reduced HbA1c by 0.7–0.9% from an average baseline of 7.9% vs. placebo (0.3% reduction) in the low‐dose cohort. Placebo‐subtracted HbA1c reductions were 0.45–0.63% (low‐dose cohort). Saxagliptin had significant placebo‐subtracted reductions in fasting serum glucose (14–25 mg/dl). Postprandial glucose levels at 60 min following a standard liquid meal test were reduced by 24–41 mg/dl vs. placebo. Saxagliptin was weight neutral. Adverse events were similar across treatment groups, including placebo, with a very low incidence of confirmed hypoglycaemia in saxagliptin treatment arms. Conclusions: Saxagliptin effectively improved glycaemic control in drug‐naive patients with T2DM and was generally safe, with a tolerability profile similar to placebo.